Genes are distributed non-randomly across the genome. One intriguing pattern to emerge from genome-wide expression profiling is that genes with sex-biased expression that is, genes that are differentially expressed between the sexes show a biased distribution on sex chromosomes. In particular, male-biased genes are depleted from the Drosophila X chromosome, such that the X has become demasculinized. The deficiency of male-biased genes can partly be explained by movement of male genes off the X chromosome. The evolutionary forces underlying these patterns are controversial and may involve male germline X inactivation, sexual antagonism, or dosage compensation mechanisms. Drosophila miranda - a species for which we recently generated a de novo genome sequence assembly - has a newly formed sex chromosome system. Its neo-Y chromosome is in transition from an ordinary autosome to a degenerate Y. In response, the neo-X is evolving the stereotypical properties of a differentiated X, including the acquisition of partial dosage compensation and - as suggested by preliminary data - an excess of gene translocations originating from its neo-X. D. Miranda therefore provides a unique system to study the mechanisms of gene trafficking on an evolving X chromosome and its evolutionary causes in action using a comparative and functional genomics approach. PUBLIC HEALTH RELEVANCE: Evidence for the importance of genetic factors in male fertility is accumulating, and is often associated with genes that are expressed in testis. Comparative genome analysis has shown that testis genes show rapid turnover between species (that is, many novel genes unique to humans show testis-specific expression) and often avoiding linkage to sex chromosomes. We will use the model species Drosophila to investigate the underlying causes for the rapid evolution of testis genes and their biased distribution in the genome, which will help to understand male infertility associated with defects in testis genes.